{"doi":"10.15252/emmm.202012871","title":"Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers","abstract":"The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we generated and integrated single-cell transcriptomic and proteomic data from multiple large pulmonary fibrosis patient cohorts. Integration of 233,638 single-cell transcriptomes (n = 61) across three independent cohorts enabled us to derive shifts in cell type proportions and a robust core set of genes altered in lung fibrosis for 45 cell types. Mass spectrometry analysis of lung lavage fluid (n = 124) and plasma (n = 141) proteomes identified distinct protein signatures correlated with diagnosis, lung function, and injury status. A novel SSTR2+ pericyte state correlated with disease severity and was reflected in lavage fluid by increased levels of the complement regulatory factor CFHR1. We further discovered CRTAC1 as a biomarker of alveolar type-2 epithelial cell health status in lavage fluid and plasma. Using cross-modal analysis and machine learning, we identified the cellular source of biomarkers and demonstrated that information transfer between modalities correctly predicts disease status, suggesting feasibility of clinical cell state monitoring through longitudinal sampling of body fluid proteomes.","journal":"EMBO Molecular Medicine","year":2021,"id":4399,"datarank":2.8082404171498254,"base_score":4.584967478670572,"endowment":4.584967478670572,"self_citation_contribution":0.687745121800586,"citation_network_contribution":2.1204952953492393,"self_endowment_contribution":0.687745121800586,"citer_contribution":2.1204952953492393,"corpus_percentile":67.29048006509358,"corpus_rank":403,"citation_count":102,"citer_count":75,"citers_with_citation_signal":62,"citers_with_endowment":62,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.648,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-03-02","fair_score":33.125,"fair_percentile":14.819700967458223,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":2925,"name":"Lukas M. Simon","orcid":"0000-0001-6148-8861","position":1,"is_corresponding":false},{"id":2926,"name":"Gabriela Leuschner","orcid":"0000-0002-4717-6922","position":2,"is_corresponding":false},{"id":537,"name":"Meshal Ansari","orcid":"0000-0002-8819-7965","position":3,"is_corresponding":false},{"id":2927,"name":"Philipp E. Geyer","orcid":"0000-0001-7980-4826","position":5,"is_corresponding":false},{"id":540,"name":"Ilias Angelidis","orcid":"0000-0002-0549-8878","position":6,"is_corresponding":false},{"id":538,"name":"Maximilian Strunz","orcid":null,"position":7,"is_corresponding":false},{"id":45213,"name":"Pawandeep Singh","orcid":null,"position":8,"is_corresponding":false},{"id":2929,"name":"Nikolaus Kneidinger","orcid":"0000-0001-7583-0453","position":9,"is_corresponding":false},{"id":2930,"name":"Frank Reichenberger","orcid":null,"position":10,"is_corresponding":false},{"id":2931,"name":"Edith Silbernagel","orcid":null,"position":11,"is_corresponding":false},{"id":2932,"name":"Stephan Böhm","orcid":"0009-0008-4376-9369","position":12,"is_corresponding":false},{"id":2933,"name":"Heiko Adler","orcid":"0000-0002-6481-6709","position":13,"is_corresponding":false},{"id":553,"name":"Michael Lindner","orcid":"0000-0002-2106-0286","position":14,"is_corresponding":false},{"id":45214,"name":"Britta Maurer","orcid":"0000-0001-9385-8097","position":15,"is_corresponding":false},{"id":2934,"name":"Anne Hilgendorff","orcid":"0000-0002-3725-996X","position":16,"is_corresponding":false},{"id":2935,"name":"Antje Prasse","orcid":"0000-0002-7336-7458","position":17,"is_corresponding":false},{"id":33096,"name":"Juergen Behr","orcid":"0000-0002-9151-4829","position":18,"is_corresponding":false},{"id":2937,"name":"Matthias Mann","orcid":"0000-0003-1292-4799","position":19,"is_corresponding":false},{"id":572,"name":"Oliver Eickelberg","orcid":"0000-0001-7170-0360","position":20,"is_corresponding":false},{"id":42,"name":"Fabian Joachim Theis","orcid":"0000-0002-2419-1943","position":21,"is_corresponding":false},{"id":573,"name":"Herbert B. Schiller","orcid":"0000-0001-9498-7034","position":22,"is_corresponding":false},{"id":2921,"name":"Janine Gote-Schniering","orcid":"0000-0001-7869-4936","position":23,"is_corresponding":false},{"id":578,"name":"Christoph H. Mayr","orcid":"0000-0001-5353-4768","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":"33650774","pmcid":"PMC8033531","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":"gold","license":"cc-by","views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":40.0,"fair_a":55.0,"fair_i":12.5,"fair_r":25.0,"fair_zscore":-1.0933,"fair_rationale":{"fair_score":33.12,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":40.0,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"datacite=0, pmcid=True, pmid=True","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers 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describe a formal protocol for access (e.g., license, authentication, or data usage policy) beyond the open access nature of the article."}]},"I":{"name":"Interoperable","score":12.5,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"linked_datasets=0, datacite=0","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"accessions=0, trials=0","rationale":null},{"key":"i_standards","label":"Standard formats, vocabularies & identifiers","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"The paper uses generic formats (e.g., count tables, MaxQuant output) and does not reference community vocabularies or standard identifiers (e.g., OBO Foundry ontologies, Cell Ontology terms) for cell types or proteins beyond standard gene symbols."}]},"R":{"name":"Reusable","score":25.0,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":0.0,"signal":"no license","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":1.0,"signal":"is_dataset","rationale":null},{"key":"r_reusability","label":"Data-availability statement, license & reproducibility","kind":"llm","weight":2.0,"fraction":0.333,"signal":null,"rationale":"The paper has a data-availability statement with repository links and is published under an open CC BY 4.0 license, but there is no explicit license for the data/code, no clear description of how to reproduce the full analysis (e.g., exact computational environment), and no detailed provenance of the reused public datasets."}]}},"suggestions":["Provide machine-readable metadata (e.g., JSON-LD or schema.org annotations) in the article HTML to describe datasets, methods, and licenses.","Include a formal data access protocol specifying conditions of use, authentication steps, and any embargo periods in the data-availability statement.","Adopt community standards such as Cell Ontology IDs for cell types and OBO ontologies for proteins, and state which standards were used in the manuscript.","Add a software environment file (e.g., conda environment.yml or Dockerfile) and a step-by-step reproducible analysis pipeline to the code repository.","Specify a clear license for the code (e.g., MIT) and datasets (e.g., CC0) in the repository, not just the 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